NEUROTROPHIN-3 INCREASES INTRACELLULAR CALCIUM IN A RAT INSULIN-SECRETING CELL-LINE THROUGH ITS ACTION ON A FUNCTIONAL TRKC RECEPTOR

Pancreatic beta cells and neuronal cells show a large number of simila rities. For example, functional receptors for nerve growth factor are present in beta cells. Here we investigate whether TrkC, a neuronal hi gh affinity receptor for neurotrophin-3, is expressed in the insulin-s ecreting cell line INS-1. We demonstrate the expression in INS-1 cells of mRNAs coding for TrkC identical in size to those found in the brai n. As in neuronal cells, different alternatively spliced forms of TrkC mRNA differing by the insertion of an alternative exon in their kinas e domain, were expressed in INS-1 cells. TrkC protein is also expresse d in INS-1 cells and is functional. Indeed, when INS-1 cells were trea ted with neurotrophin-3, TrkC became phosphorylated on tyrosine residu es, and the expression of early response genes was induced. This activ ation of the receptor was paralleled by a rapid and transient increase in cytosolic free calcium due to an influx of extracellular calcium. Functional receptors for NT-3 are thus expressed in INS-1 cells. This cell line provides a new model for the study of NT-3 signal transducti on and should be useful in the understanding of the role of neurotroph ins in insulin-secreting cells.